Longevity 2023: …to X, Y, Z

Our second look at some of 2023’s longevity news, but this time from the other end of the alphabet, including XPRIZE, young blood and Zero.

Earlier in the week, we took a spin through a selection of longevity stories that had the letter A in common; as the year draws to a close, it’s time to flip to the other end of the alphabet and check out some of the X, Y and Z stories we published this year.

X is for Xenotransplantation

Xenotransplantation comes of age
CRISPR-edited porcine kidney survived and supported life for 758 days in non-human primates.
Photo: eGenesis

Publishing in Nature, US biotech eGenesis disclosed long-term survival data from a proof-of-concept study, demonstrating the viability of genetically engineered donor kidneys from pigs transplanted into monkeys. The study increased hopes that xenotransplantation – transplanting organs from an animal source into a human recipient – may soon enter human trials and constituted the largest and most comprehensive preclinical dataset published in a domain where recipient survival has typically been limited to weeks or months.

“If you look at pig kidney transplants into primates over the past several decades, rarely do you see something break 100 days’ survival,” eGenesis CEO Mike Curtis told Longevity.Technology. “Now we’re talking about a donor that addresses all the challenges of xenotransplantation cross species and produces long term outcomes … We now have seven recipients that have made it out to that 12-month endpoint, which is unique in the field.”

X is for XPRIZE

Could XPRIZE Healthspan deliver the ‘holy grail’ for longevity science?
Jamie Justice and Peter Diamandis discuss the launch of XPRIZE Healthspan at the the Global Healthspan Summit in Riyadh, Saudi Arabia

One of the highlights of the  Global Healthspan Summit in Riyadh was the announcement of  XPRIZE Healthspan – a whopping $101 million in prize money to a team that successfully develops a therapeutic that restores muscle, cognition and immune function by 20 years in older adults. The winning team must also be able to demonstrate the results in a treatment period of one year or less.

“This is key for the longevity field – our framework is about functional improvement,” XPRIZE Healthspan’s executive director Dr Jamie Justice told Longevity.Technology. “We’re focusing on function, because we’re asking teams to show improvement, which is very different than something like the TAME trial, which is looking at prevention. We have a ‘menu’ of possible measures that people can use under the three domains of muscle, cognitive and immune function. We want teams to have a strong signal and show that they’ve made change in a meaningful way across all three domains.”

Y is for Yamanaka Factors

Is the reversal of cellular aging possible through chemical means?

Discovery of the Yamanaka Factors, the product of a group of genes that have a profound effect on cellular aging, won Shinya Yamanaka the Nobel Prize in 2012. The discovery that mature cells can be reprogrammed to become pluripotent has catalyzed cellular reprogramming research, and while there are still safety and delivery hurdles to overcome, this year saw several promising developments.

In April, researchers at Life Bio and academic researchers, including Drs Bruce Ksander and David Sinclair, reported that Life Bio’s therapy significantly restored visual function in an non-human primate model of non-arteritic anterior ischemic optic neuropathy (NAION), a disorder similar to a stroke of the eye that is characterized by painless yet sudden loss of vision. LifeBio’s lead platform reprograms the epigenome of older animals to resemble that of younger animals via expression of three Yamanaka factors, Oct4, Sox2, and Klf4, and there was much excitement about the success of the therapy in primates.

Then in July, a new study in Aging undertook to identify molecules that can reverse cellular aging and rejuvenate human cells without altering the genome. The researchers identified six chemical cocktails that could reverse transcriptomic age and rejuvenate cells to the same extent as overexpression of Yamanaka Factors, successfully demonstrating that rejuvenation by age reversal can be achieved, not only by genetic, but also chemical means.

Y is for Young Blood and Yuvan

Young blood rising: new plasma therapy moves closer to the clinic

Blood transfusions, parabiosis, plasma fraction treatments and plasma-inspired therapeutics have made headlines and raised eyebrows in equal measure. Back in February, Dr Harold Katcher did both when his E5 young plasma-mimicking therapeutic, which he developed with a team at California-based startup Yuvan, extended the lifespan of the world’s longest living lab rat to an incredible 47 months. The equivalent in human years is the grand old age of 126.

Yuvan went on to publish a preprint revealing that its mysterious E5 therapy is actually derived from pig plasma and claiming that it “markedly reverses aging in rats according to epigenetic clocks, IgG glycans, and other biomarkers of aging.” Having demonstrated its lifespan-improving effects in rats, the next stage for Yuvan is to see if E5 also works in larger mammals. The company’s next trial, expected to begin imminently, will be in 10-year-old dogs.

“Our secondary endpoints will include a lot of those biomarkers that we tested in the rats, because we want to see how they compare in a much larger mammal,” Yuvan co-founder Akshay Sanghavi told Longevity.Technology. “This should give us a very big hint about what might happen in humans.”

Z is for Zuzalu

Zuzalu: a pop-up city with longevity at its heart
Photograph: Elizaveta Galitckaia/Shutterstock

Running from March to May this year, Zuzalu hosted a two-month experiment dubbed the First Longevity City. The brainchild of Ethereum founder Vitalik Buterin, Zuzalu is played host to a variety of events on topics like synthetic biology, technology for privacy, public goods, governance, and, of course, longevity. The longevity component of the Zuzalu experiment was supported by the longevity-focused decentralized organization VitaDAO, and head of deal flow Laurence Ion, told Longevity.Technology the project was centered on bringing bright minds together and seeing what happens from there.

“We’ve been supporting healthy co-living – like having a restaurant with a healthy food menu, having accountability partners, working out together, doing cold plunges, and so on,” says Ion. “We’re also tracking biomarkers, like continuous glucose monitoring, biological age tests, and blood tests that also calculate phenotypic age. Imagine if this was a permanent thing and being done across thousands of people instead of hundreds, enabling decentralized clinical trials?” 

Z is for Zero

'We all play don't die every day – now let's get really good at it'
Photograph: Magdalena Wosinska

Bryan Johnson, longevity enthusiast and perhaps the world’s most famous biohacker published a book entitled Don’t Die this year. Johnson, who is on a mission to maximally reverse the quantified biological age of each of his 70 organs, extending both his lifespan and healthspan, assumed the nom de plume of Zero for this venture, which is rather like a longevity-focused Pilgrim’s Progress. Zero is described in the book as the “first individual H. sapiens to surpass five hundred years of age,” who dies in 2478 (in an accident, rather than from old age), just weeks away from “becoming Homo Deus.”

Don’t Die by Zero will be available on Amazon as both a printed version and an audiobook in the future, but the free, downloadable ebook will remain on Johnson’s website. Johnson told Longevity.Technology Don’t Die is an effort to try to strike up a fresh conversation – what now? “It basically tries to fill a void saying that the structures of society today, from capitalism to religions, really don’t offer meaningful things to say right now, that ideologically they are not up to this … What does it mean to be human right now, what if you could access an algorithm that would allow you to achieve near-perfect health, what do you owe to your future self? How can we emotionally process all the complicated questions we’re up against? The book tries to capture that essence, told through characters of myself.”